Approximately 1/50 individuals in the US are carriers for the defect phenylalanine hydroxylase which, in the homozygous, results in the disease phenylketonuria (PKU). Patients with PKU suffer from developmental abnormalities related to the central nervous system. Females with PKU who become pregnant require strict dietary control of phenylalanine since high levels of blood phenylalanine, or its metabolites, result in various degrees of fetal abnormalities. The introduction of aspartame (L-aspartyl-L-phenylalanine-alphamethyl ester) for consumption by the general population, may increase health hazards if long term use affects the activity of phenylalanine hydroxylase or if the additional load of phenylalanine from aspartame is diverted to other metabolites such as phenylethylamine and other aromatic acids of phenylalanine. The population that will be most vulnerable to the effects of aspartame would be carriers for PKU, notably females. Obviously, most such females will not know of their carrier state. The danger for such females would be an increase in blood levels of phenylalanine and its metabolites during pregnancy, which may lead to developmentally delayed or mentally retarded individuals. Indeed, the effects of aspartame may also occur in younger individuals, specifically carriers for PKU. In these cases an increase in the levels of phenylalanine metabolites may lead to behavior problems and learning disabilities. It is proposed to study the effects of long term aspartame intake on levels of phenylethylamine, the aromatic acids of phenylalanine and tyrosine and the effect of such intake on the in vivo activity of phenylalanine hydroxylase in normal individuals, obligate carriers for PKU and patients with benign hyperphenylalaninemia. Benign hyperphenylalaninemia does not require dietary restriction of phenylalanine and the carrier frequency for this defect is estimated to be 1/70. Individuals enrolled in the study will be given, for 12 weeks, aspartame in doses corresponding to, or higher than the projected daily use. Assays of in vivo phenylalanine hydroxylase activity will be based on measurement in the plasma of the conversion of d5-phenylalanine to d4-tyrosine. Blood and urine phenylalanine, tyrosine, phenylethylamine, the organic acids of phenylalanine and tyrosine, such as phenylpyruvic, phenyllactic, and phenylacetic acids will be measured. Since the total amino acid analysis will be performed on each sample, other amino acids that are of interest such as aspartic, glutamic, tryptophan and the branched chain amino acids will be studied throughout the trial period.